Top PDF Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

Wilson’s disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson’s disease ever reported of 1:1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (1861 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson’s disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson’s disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.
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SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype-Phenotype Correlations

SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype-Phenotype Correlations

Four cohorts were included in the study. The first cohort (group 1) included 143 clinically well-characterized patients with NS enrolled in research protocols. Nearly all subjects of this cohort were of European ancestry, with the majority being Italian. Within this group, subjects were assessed by clinical geneticists experienced with NS and clinically related disorders (G.Z., M.C.D., L.M., B.D., G.B.F., M.C.S., A.S., I.K., G.N., M.F.F., A.P., F.S. and O.G.). Clinical assessment included physical, anthropometric, neurologic, and cardiac evaluations, as well as accurate examination for craniofacial features, ophthalmologic, and otorhinolaryngologic defects, and ectodermal and musculoskeletal anomalies. Clinical features for the majority of these individuals satisfied diagnostic criteria reported for NS [van der Burgt et al. 1994], but a few individuals with a highly suggestive phenotype who lacked sufficient features to receive a definitive diagnosis were also included. Based on scanning of the coding exons by denaturing high-performance liquid chromatography (DHPLC) analysis and/or direct sequencing, no subject within this cohort harbored a mutation in PTPN11, KRAS, or RAF1. For approximately half of the cases, mutations in BRAF, MAP2K1, SHOC2, CBL, and NRAS had also been excluded. Besides this large cohort, nine subjects with features fitting CFCS and no mutation in KRAS, BRAF, MAP2K1, or MAP2K2 (group 2) [Sarkozy et al., 2009a] were also included in the study. The third cohort (group 3) (N 5 358) comprised anonymous samples from individuals with phenotypes suggestive of NS for whom commer- cial DNA diagnostic testing was performed. Clinical data were not available for these patients, and PTPN11 mutations had not systematically been excluded in all the subjects included in this group. Although the output obtained from genotyping this cohort of subjects could not be used in genotypephenotype correlation studies or to estimate SOS1 mutation prevalence in the NS population, the mutation data were utilized to provide a more detailed picture about the molecular spectrum of disease-causing mutations affecting the SOS1 gene. Finally, a cohort of 59 subjects with nonsyndromic CHDs (PS, N 5 21; atrial septal defects (ASDs), N 5 23; ventricular septal defects (VSDs), N 5 15) was included in the study (group 4). Clinical assessment of patients with isolated CHDs included complete physical evaluation of dysmorphism and malformations, anthropometric measurements, renal ultrasonography, and radiological studies. Cardiac evaluation included preoperative physical evaluation, chest X-ray film, 12-lead electrocardiogram, and two-dimensional transthoracic echocardio- graphy with color flow Doppler. Karyotype analysis was performed in all patients of this cohort. Inclusion criteria were based on the
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Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.

Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.

The present study of KCNQ4 mutations was carried out to 1) determine the prevalence by unbiased population-based genetic screening, 2) clarify the mutation spectrum and genotype/phenotype correlations, and 3) summarize clinical characteristics. In addition, a review of the reported mutations was performed for better understanding of this deafness gene. The screening using 287 probands from unbiased Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL) families identified 19 families with 7 different disease causing mutations, indicating that the frequency is 6.62% (19/287). While the majority were private mutations, one particular recurrent mutation, c.211delC, was observed in 13 unrelated families. Haplotype analysis in the vicinity of c.211delC suggests existence of a common ancestor. The majority of the patients showed all frequency, but high-frequency predominant, sensorineural hearing loss. The present study adds a new typical audiogram configuration characterized by mid-frequency predominant hearing loss caused by the p.V230E mutation. A variant at the N-terminal site (c. 211delC) showed typical ski-slope type audiogram configuration. Concerning clinical features, onset age was from 3 to 40 years old, and mostly in the teens, and hearing loss was gradually progressive. Progressive nature is a common feature of patients with KCNQ4 mutations regardless of the mutation type. In conclusion, KCNQ4 mutations are frequent among ADNSHL patients, and therefore screening of the gene and molecular confirmation of these mutations have become important in the diagnosis of these conditions.
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Communities of parasite metazoans in Piaractus brachypomus (Pisces, Serrasalmidae) in the lower Amazon River (Brazil)

Communities of parasite metazoans in Piaractus brachypomus (Pisces, Serrasalmidae) in the lower Amazon River (Brazil)

The aim of this study was to investigate the component community of parasite metazoans of Piaractus brachypomus in the lower Amazon River, northern Brazil. From 34 necropsied fish, 27,384 metazoan parasites were collected, such as Anacanthorus spathulatus, Mymarothecium viatorum and Notozothecium janauachensis (Monogenoidea); Spectatus spectatus and Contracaecum sp (Nematoda); Clinostomum marginatum and Dadaytrema oxycephala (Digenea); and Argulus carteri and Ergasilus sp. (Crustacea). The dominant species was S. spectatus followed by monogenoidean species, and there was aggregated dispersion of parasites, except for D. oxycephala and Contracaecum sp., which presented random dispersion. Positive correlation among the abundance of the three monogenoideans species were found, thus indicating that there was no competition between the species of these parasites on the gills of hosts. The abundances of some parasite species showed positive correlations with the size of the hosts, but the condition factor of the fish was not affected by the parasitism levels. It showed that this host had a metazoan community characterized by high species richness of metazoans, low evenness and high diversity of parasites, with prevalence of endoparasites, including larval stages. This was the first record of C. marginatum, A. carteri, Ergasilus sp. and Contracaecum sp. for P. brachypomus.
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André Marubayashi Hidalgo1 , Elias Nunes Martins2 , Alexandre Leseur dos Santos

André Marubayashi Hidalgo1 , Elias Nunes Martins2 , Alexandre Leseur dos Santos

At the end of the trial performance data was obtained from 628 birds (82 red line, 152 blue line and 212 yellow line, all laying lines) and 182 meat line birds. The performance data collected were mean egg weight (g) in two weighings, the first at 70 days and the second at 120 days; total egg production in 189 days; and age at first egg. Evaluations were performed using the software MTGSAM - Multiple Trait Gibbs Sampling in Animal Models (Van Tassel & Van Vleck, 1995), which proceeds from Bayesian estimation using the Gibbs sampling technique, applied to a three-trait animal model as follows.
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APOL1 risk variants and kidney disease: what we know so far

APOL1 risk variants and kidney disease: what we know so far

challenge for a specialized cell such as the podocyte, responsible for maintaining all glomerular filtration surface covered with its foot processes, inevitably causing stress on the entire system. This data supports the hypothesis that AA individuals with HRG have an inadequate number of podocytes for their age. Lower podocytes density can represent a risk factor predisposing individuals to glomerular diseases, since a kidney would further reduce the podocyte reserve, leading to ESRD. Following this model, the survival of glomeruli in sufficient numbers throughout life will depend on the total cumulative loss of podocytes, the increased glomerular volume and the ability of the remaining podocytes to adapt to the stress resulting from the fall of podocyte density. 59 Another study in
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Rev. Bras. Hematol. Hemoter.  vol.25 número3

Rev. Bras. Hematol. Hemoter. vol.25 número3

Fanconi anaemia (FA) is an autosomal recessive disorder associated with a very high frequency of bone marrow failure, developmental abnormalities, such as aplasia of the thumb and radius, growth retardation, Fig. 1 – Chromosome spreads showi n g typi cal chromosome breaks (arrows) i n the Fan con i an aemi a pati en t an alysed by the di epoxybutan e test

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MORPHOMETRY AND VARIATIONS OF MALLEUS WITH CLINICAL CORRELATIONS

MORPHOMETRY AND VARIATIONS OF MALLEUS WITH CLINICAL CORRELATIONS

The st udy from Indian subcont inent t hough had done on m alleus m orphom et ry; west erners have done t he st udy using m or e m or phom et r ic param et ers. The param et ers of t he m alleus st udied include t ot al lengt h (m axim al dist ance bet w een t he t op of t he head and t he end of t he handle), lengt h of handle (dist ance from t he end of t he lat eral process t o t he end of handle) and lengt h of head and neck (m axim al dist ance bet w een t he t op of t he head and t he end of t he lat eral process). Vincent iis & Cim ino st udied m alleus from infant s, juvenile, adult m ale & fem ales. They h av e repo r t ed a di f f er en ce bet w een right and left m alleus. In our st udy t h er e w as n o si gn if icant d if fer en ce n ot ed bet w een m ale and fem ale m alleus. This is in accordance w it h m any previous st udies [13,14]. Our st udy goes in cont rast w it h anot her st udy from Indian subcont inent in w hich 60 m alleus show ed skew ed m or ph ology of m al es and females m alleus [15]. The m orphomet ric analysis of m alleus m ay help in underst anding various m i dd l e ear p at ho l o gi es. It m ay ai d t h e ot orhinolaryngologist s in ossicular replacem ent surgeries.
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APOL1 risk variants and kidney disease: what we know so far

APOL1 risk variants and kidney disease: what we know so far

challenge for a specialized cell such as the podocyte, responsible for maintaining all glomerular filtration surface covered with its foot processes, inevitably causing stress on the entire system. This data supports the hypothesis that AA individuals with HRG have an inadequate number of podocytes for their age. Lower podocytes density can represent a risk factor predisposing individuals to glomerular diseases, since a kidney would further reduce the podocyte reserve, leading to ESRD. Following this model, the survival of glomeruli in sufficient numbers throughout life will depend on the total cumulative loss of podocytes, the increased glomerular volume and the ability of the remaining podocytes to adapt to the stress resulting from the fall of podocyte density. 59 Another study in
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Arq. NeuroPsiquiatr.  vol.71 número8

Arq. NeuroPsiquiatr. vol.71 número8

he article by Bem, Raskin, Muzzilo et al. (Wilson’s disease in Southern Brazil: genotype- phenotype correlation and description of two novel mutations in ATP7B gene) in this issue addresses the frequency of mutations in Southern Brazil in which a population of European ancestry predominates 7 . A total of 36 subjects with clinical diagnosis of WD were studied and

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Genotype-phenotype correlation in Brazillian Rett syndrome patients

Genotype-phenotype correlation in Brazillian Rett syndrome patients

(3.65% of all variations), previously described, and an alter- ation whose pathogenicity was not been previously deter- mined were also found (1.1% of all variations). Six patients had only non-pathogenic variations (5.8%). C to T transitions at CpG islands totalizes 88.1% (74/84). Most of the patho- genic point mutations were concentrated on the meth- yl binding domain (MBD) (25/66 – 36%). The frequency of pathogenic point mutations was 64.1% (66/103). The distri- bution of pathogenic point mutations is shown in Figure 2. Three patients deserve special consideration. Two were atypical, one had hyperchromic linear spots and normal karyotype and the other had a chromosomal ab- normality, t(4)(q11);14(q11). None of them had any detect- ed point mutation. The third patient had a classical phe- notype but high levels of lactic and pyruvic acids. This pa- tient had the T158M mutation, previously described. All were included because it was considered interesting to check if they had MECP2 mutations.
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Frequency of TGF-beta and IFN-gamma Genotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients

Frequency of TGF-beta and IFN-gamma Genotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients

Kopp et al. also related that increased levels of circulating TGF- �1 induced progressive renal disease characterized by mesangial expansion, accumulation of glomerular immune deposits and matrix proteins, and interstitial ibrosis in this transgenic mouse model suggesting that chronically elevated circulating levels of TGF-�1 induce progressive glomeru- losclerosis [15]. herefore, it appears that renal diseases may also result from the inlammation and from inappropriate regulation of TGF- � expression [ 17]. However, until this moment there is no data about the role of IFN- � and TGF- � in critically ill patients as risk markers to AKI. Recently, the study of polymorphisms of genes involved in host immune response, including cytokines and other modulators of the inlammatory response, has been a subject of interest, since these genetic markers may be potential determinants of susceptibility to or severity of acute events such as AKI [18, 19]. he reason why some patients with SIRS develop AKI and others do not is still unclear. So, it is possible that polymor- phisms of inlammatory cytokines genes, in particular IFN- � and TGF- �, may be involved in the pathophysiology of AKI in critically ill patients.
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Aspectos epidemiológicos da infecção pelo vírus da Hepatite C e coinfecções com os vírus B e Delta no Estado do Acre, Amazônia ocidental brasileira

Aspectos epidemiológicos da infecção pelo vírus da Hepatite C e coinfecções com os vírus B e Delta no Estado do Acre, Amazônia ocidental brasileira

High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia... High prevalence of hepatitis B, C and delta viru[r]

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Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

A study of the mutations found in 245 patients originating from 24 different coun- tries showed that FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C with a later onset of aplas- tic anemia, and FA-A patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an al- tered protein, indicating that patients with specific mutations in the FANCA and FANCG genes are in a high-risk group with a poor hematologic outcome and should be consid- ered to be candidates both for frequent moni- toring and early therapeutic intervention (13,21).
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Rev. bras. epidemiol.  vol.14 número4

Rev. bras. epidemiol. vol.14 número4

In addition to the high prevalence of inadequate work ability, a significant number of professionals had high levels of fatigue (25.7%). It should be emphasized that fatigue has been identified as a factor that contributes to accidents and diseases in several work sectors, including hospitals, especially when long and irregular work- ing hours are performed. Certain effects of fatigue, such as the increase in reaction time, lack of attention in the workplace, and adoption of inadequate strategies to perform work activities have been identified as causes of work-related accidents 30 .
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A diarrheal disease surveillance system in Cali, Colombia : Theoretical basis and methods

A diarrheal disease surveillance system in Cali, Colombia : Theoretical basis and methods

2) Outbreak investigation findings. 3) Large incidence or prevalence surveys of endemic disease in defined population. 4) Laboratory surveillance of environ- mental s[r]

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Dement. neuropsychol.  vol.8 número4

Dement. neuropsychol. vol.8 número4

One hundred and twenty high school students were trained, twice a week, for three months. Upon comple- tion of the training, 88 pupils were able to administer the survey questionnaire to individuals over 60 in the catchment area. he population was made aware about the survey through local media ads, lyers and pre- survey visits. On the day of the survey, the students bearing identity badges and covered by insurance, per- formed the survey from 8 am to 4 pm, house by house in the catchment area. In this door-to door survey, 4,768 households were visited where 3,122 individuals over 60 were contacted, 1,526 of whom agreed to complete the survey. After exclusion of 73 forms (incomplete or illegible), the inal sample comprised 1,453 interviews.
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J. bras. psiquiatr.  vol.64 número3

J. bras. psiquiatr. vol.64 número3

Objective: To evaluate, in a community sample of adolescents, the presence of comorbidi- ties in different anxiety disorders. Methods: This is a cross-sectional study, initially composed of 2,457 adolescents, aged between 10-17 years old, from public schools of the area covered by the Basic Health Unit of a university hospital. We applied the Screen for Child Anxiety Rela- ted Emotional Disorders (SCARED) to assess for anxiety disorders. Then, 138 positive cases in the screening were assessed for mental disorders through the Schedule for Affective Disor- der and Schizophrenia for School-Age Children – Present and Lifetime Version (K-SADS-PL). Results: Patients with anxiety disorders had more association with other anxiety disorders, as well as depression, and enuresis. The most common comorbidity described in our study was between generalized anxiety disorder and separation anxiety disorder (OR = 4.21, 95% CI 1.88, 9.58). Significant association was observed between other disorders such as enure- sis and separation anxiety disorder (OR = 3.81, 95% CI 1.16, 12.49), as well as depression and generalized anxiety disorder (OR = 3.40; 95% CI 1.52, 7.61). Conclusion: Our study showed a relevant presence of comorbidities adolescents with anxiety disorders, selected from a com- munity sample, especially regarding other anxiety disorders. Nevertheless, further studies are needed to confirm our findings.
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Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

Host genes related to paneth cells and xenobiotic metabolism are associated with shifts in human ileum-associated microbial composition.

Paneth cells. We therefore selected gene transcripts within these three microarray clusters for further analysis. These genes included the alpha defensins and members of the regenerating gene (REG) family. The alpha defensins are antimicrobial peptides that are secreted by Paneth cells. Manipulation of alpha defensin expression in experimental animals has been shown to alter gut microbial composition [43]. On the other hand, monoassociation of a Bacteroidetes species with germ free animals was shown to alter regulation of Paneth cell gene expression [44]. Altered expression of alpha defensins have been associated with the ileal Crohn’s disease phenotype. The REG genes belong to the calcium (C-type) dependent lectin superfamily and have been noted to be upregulated in CD and UC intestinal tissues [45], [46]. Expression levels of cellular detoxification genes, which are target genes for the transcription factor pregnane X receptor (PXR and also termed NR1I2), have been previously noted to be down-regulated in the colons of UC patients [41]. The expression levels of these genes were correlated with bacterial genera that had been previously reported to be disease associated [42]. At a threshold of P #0.05, exploratory analyses revealed potential correlations between transcript levels of specific genes with individual bacterial genera (e.g. Faecalibacterium, Bacteroidetes and Parabacteroides), that were modulated by disease phenotype. By honing in on these promising correlations identified by exploratory studies, we hope to be able to further confirm these observations in an expanded set of samples. Co-linearity between input variables may occur, despite our efforts to shrink the dimensions of the datasets. This may account for why C. difficile was not selected in this subset of the microbial dataset. Alternatively C. difficile may not have been selected because paired microarray and microbial data have been collected on a smaller number of subjects thus far. While the use of immunomodulators and anti-TNFa biologics were included as co- variates in the MANOVA [24], we cannot completely exclude the potential confounding effects of these drugs on the microbial composition and mucosal gene expression. Nevertheless our results demonstrate that integrating paired expression profiles and microbial data can lead to the discovery of biologically meaningful host-microbial interactions in inflammatory bowel diseases. We anticipate that as we expand the sample set, other associations will be detected.
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Arq. NeuroPsiquiatr.  vol.59 número3B

Arq. NeuroPsiquiatr. vol.59 número3B

ABSTRACT - Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia and presents great phenotypic variability. MJD presenting with spastic paraparesis was recently described in Japanese patients. We report the case of 41-year-old woman with the phenotype of complicated hereditary spastic paraplegia. Her father died at the age of 56 years due to an undiagnosed progressive neurological disease that presented parkinsonism. She had an expanded allele with 66 CAG repeats and a normal allele with 22 repeats in the gene of MJD. MJD should be considered in the differential diagnosis of autosomal dominant complicated HSP. A patient with the phenotype of complicated HSP and relatives with other clinical features of a neurodegenerative disease should raise the suspicion of MJD.
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